tbuckley/cabot-search huggingface dataset:
Aerosol deposition in mechanically ventilated patients. Optimizing nebulizer delivery.
Authors: T G O'Riordan, L B Palmer, G C Smaldone
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Previous studies have suggested that nebulizers are inefficient in delivering aerosolized medication to the lung in patients supported by mechanical ventilation. In a recent bench study, we characterized factors that may affect aerosol delivery, i.e., nebulizer type, ventilator settings (duty cycle), volume fill, and humidification as well as technical factors affecting measurement of deposition (e.g., radiolabeled compounds). Utilizing the predictions from our bench data, the present study was designed to assess nebulized aerosol delivery to ventilated patients under optimal conditions. Seven patients who were receiving mechanical ventilation (Bear II) via tracheostomy tube (TT) were studied. The humidifier was turned off. The test aerosol, a saline solution labeled with 99mTechnetium bound to human serum albumin (99mTc-HSA), was administered via a jet nebulizer (AeroTech II, 1.1 +/- 1.8 microns [mass median aerodynamic diameter, MMAD, geometric standard deviation, sigma g]), which was incorporated into the ventilator circuit and run to dryness. Inhaled and deposited radioactivity were measured by a mass balance/filter technique. TT versus lung deposition were quantified by removal of the inner cannula and direct measurement of TT deposition in a well counter. Inspiratory versus expiratory components of TT deposition were separated via bench techniques for each TT tube and breathing pattern. The regional distribution of deposited radioactivity was confirmed by gamma camera scans before and after TT removal. Measured radioactivity at each site was expressed as a percentage of nebulizer charge (i.e., the quantity of radioactivity originally placed in the nebulizer). On average, 30.6 +/- 6.3% (SD) of the charge was inhaled by the ventilated patients. Mean deposition in the TT during inspiration was 2.6 +/- 0.5%.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacogenomic Biomarkers for Prediction of Severe Adverse Drug Reactions
Authors: Magnus Ingelman-Sundberg
Journal: New England Journal of Medicine (2008)

The accumulating knowledge of human genomic variation is being used for the development of personalized medicine, with the aims of decreasing the number of adverse drug reactions and increasing the efficacy of drug treatment. Considerable pharmacogenomic research has focused on understanding the molecular mechanisms behind adverse drug reactions and finding biomarkers that identify people at risk.Serious adverse drug reactions have been shown to cause or contribute to 6 to 7% of all hospitalizations, a 2-day increase in the average length of hospitalization, and 100,000 deaths annually in the United States — and may, according to some estimates, cost about . . .
Accuracy of Peripheral Thermometers for Estimating Temperature
Authors: Daniel J. Niven, Jonathan E. Gaudet, Kevin B. Laupland, Kelly J. Mrklas, Derek J. Roberts, Henry Thomas Stelfox
Journal: Annals of Internal Medicine (2015)

Background: Body temperature is commonly used to screen patients for infectious diseases, establish diagnoses, monitor therapy, and guide management decisions. Purpose: To determine the accuracy of peripheral thermometers for estimating core body temperature in adults and children. Data Sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL Plus from inception to July 2015. Study Selection: Prospective studies comparing the accuracy of peripheral (tympanic membrane, temporal artery, axillary, or oral) thermometers with central (pulmonary artery catheter, urinary bladder, esophageal, or rectal) thermometers. Data Extraction: 2 reviewers extracted data on study characteristics, methods, and outcomes and assessed the quality of individual studies. Data Synthesis: 75 studies (8682 patients) were included. Most studies were at high or unclear risk of patient selection bias (74%) or index test bias (67%). Compared with central thermometers, peripheral thermometers had pooled 95% limits of agreement (random-effects meta-analysis) outside the predefined clinically acceptable range (± 0.5 °C), especially among patients with fever (−1.44 °C to 1.46 °C for adults; −1.49 °C to 0.43 °C for children) and hypothermia (−2.07 °C to 1.90 °C for adults; no data for children). For detection of fever (bivariate random-effects meta-analysis), sensitivity was low (64% [95% CI, 55% to 72%]; I 2 = 95.7%; P < 0.001) but specificity was high (96% [CI, 93% to 97%]; I 2 = 96.3%; P < 0.001). Only 1 study reported sensitivity and specificity for the detection of hypothermia. Limitations: High-quality data for some temperature measurement techniques are limited. Pooled data are associated with interstudy heterogeneity that is not fully explained by stratified and metaregression analyses. Conclusion: Peripheral thermometers do not have clinically acceptable accuracy and should not be used when accurate measurement of body temperature will influence clinical decisions. Primary Funding Source: None.
The Therapeutic Orientation to Clinical Trials
Authors: Franklin G. Miller, Donald L. Rosenstein
Journal: New England Journal of Medicine (2003)

Traditionally, clinical trials have been understood as continuous with clinical medicine.1 In providing medical care for patients, the physician makes observations, investigates, tests hypotheses, and experiments with different treatments. Moreover, the exemplary physician is always learning how to improve treatment for future patients on the basis of clinical experience with current patients and familiarity with the medical literature. Chalmers summarized this view as follows: "The practice of medicine is in effect the conduct of clinical research . . . . Every practicing physician conducts clinical trials daily as he is seeing patients. The research discipline known as the `clinical trial' . . .
A randomized trial of alternating chemotherapy versus best supportive care in advanced non-small-cell lung cancer.
Authors: R Cellerino, D Tummarello, F Guidi, P Isidori, M Raspugli, B Biscottini, G Fatati
Journal: Journal of Clinical Oncology (1991)

From April 1985 to September 1988, 128 patients with advanced non-small-cell lung cancer (NSCLC) were enrolled in a prospective randomized trial evaluating chemotherapy (arm A) versus best supportive care (arm B). Chemotherapy consisted of cyclophosphamide 500 mg/m2 intravenously (IV) day 1, epirubicin 50 mg/m2 IV day 1, and cisplatin 80 mg/m2 IV day 1 (CE'P regimen) alternating every 4 weeks with methotrexate 30 mg/m2 IV day 1, etoposide 200 mg/m2 IV day 1, and lomustine (CCNU) 70 mg/m2 orally day 1 (MEC' regimen) until progression. Of the 123 patients (62 treated and 61 controls) eligible for survival, 115 were fully evaluable for response (58 treated and 57 controls). Response rates were 21% partial response, 53% stable disease, and 26% progressive disease in arm A, and 47% stable disease and 53% progressive disease in arm B. Median survival was 34.3 weeks (range, 4.3 to 218.6+ weeks) in arm A versus 21.1 weeks (range, 4.3 to 188.6 weeks) in arm B; the difference was not significant at P = .153 (Mantel-Cox). Subgroups of patients retrospectively analyzed by age, performance status, stage M0/M1, and weight loss or not showed no significant difference in survival. Poor-risk patients (at least two of the following: poor performance status, stage M1, weight loss) of arm A survived significantly longer than poor-risk patients of arm B (23.6 weeks v 12.4 weeks, Mantel-Cox P = .008); a significant difference in survival was also observed between nonsquamous cell patients of arm A and those of arm B (median survival, 38.6 weeks v 16.7 weeks; Mantel-Cox P = .041). Toxicity on the chemotherapy arm was hematologic (World Health Organization [WHO] grade greater than 3) in 12% of CE'P and in 13% of MEC' courses and gastroenteric (WHO grade greater than 3) in 24% of CE'P courses and in 8% of MEC' courses. Our alternating treatment was not significantly superior to supportive care. It is likely that certain subgroups of the NSCLC category may have an advantage with chemotherapy.
Direct Cardiac Reprogramming
Authors: Taketaro Sadahiro, Shinya Yamanaka, Masaki Ieda
Journal: Circulation Research (2015)

The discovery of induced pluripotent stem cells changed the field of regenerative medicine and inspired the technological development of direct reprogramming or the process by which one cell type is directly converted into another without reverting a stem cell state by overexpressing lineage-specific factors. Indeed, direct reprogramming has proven sufficient in yielding a diverse range of cell types from fibroblasts, including neurons, cardiomyocytes, endothelial cells, hematopoietic stem/progenitor cells, and hepatocytes. These studies revealed that somatic cells are more plastic than anticipated, and that transcription factors, microRNAs, epigenetic factors, secreted molecules, as well as the cellular microenvironment are all important for cell fate specification. With respect to the field of cardiology, the cardiac reprogramming presents as a novel method to regenerate damaged myocardium by directly converting endogenous cardiac fibroblasts into induced cardiomyocyte-like cells in situ. The first in vivo cardiac reprogramming reports were promising to repair infarcted hearts; however, the low induction efficiency of fully reprogrammed, functional induced cardiomyocyte-like cells has become a major challenge and hampered our understanding of the reprogramming process. Nevertheless, recent studies have identified several critical factors that may affect the efficiency and quality of cardiac induction and have provided new insights into the mechanisms of cardiac reprogramming. Here, we review the progress in direct reprogramming research and discuss the perspectives and challenges of this nascent technology in basic biology and clinical applications.
EGFR Tyrosine Kinase Inhibition Worsens Acute Lung Injury in Mice with Repairing Airway Epithelium
Authors: Chika Harada, Tomonobu Kawaguchi, Saiko Ogata-Suetsugu, Mizuho Yamada, Naoki Hamada, Takashige Maeyama, Ryota Souzaki, Tatsuro Tajiri, Tomoaki Taguchi, Kazuyoshi Kuwano, Yoichi Nakanishi
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Epidermal growth factor receptor (EGFR) and its ligands play important roles in the regeneration of damaged epithelium and proliferation of various epithelial tumors. Although the EGFR-tyrosine kinase inhibitor gefitinib is effective against advanced non–small cell lung cancer with EGFR mutations, some patients treated with this agent develop severe acute interstitial pneumonia. Characteristics of patients who develop interstitial pneumonia include older age, smoking history, and preexisting interstitial pneumonia suggesting a connection between airway injury and alveolar dysfunction.Objectives: The purpose of this study was to investigate the effects of gefitinib on airway repair after injury.Methods: C57BL/6J mice received intraperitoneally naphthalene at Day 0. Gefitinib (20, 90, or 200 mg/kg) was given daily at Days −1 to 13 after naphthalene administration. Bronchoalveolar lavage fluid and lung tissue were obtained at Days 7 and 14. Terminal bronchial epithelial cells from Days 7 and 14 were retrieved with laser capture microdissection, and gene expression analyzed using microarray.Measurements and Main Results: Gefitinib treatment after naphthalene prolonged neutrophil sequestration and worsened acute lung injury. We found 17 genes with more than a threefold increase in bronchiolar epithelial cells from mice treated with 200 mg/kg of gefitinib after naphthalene at Day 14 compared with those treated with naphthalene alone. Up-regulated genes included S100A8, S100A6, and StefinA3. These genes are known to participate in neutrophil sequestration, acute inflammation, and airway remodeling.Conclusions: EGFR inhibition in repairing airway epithelial cells modulated significant expression of genes involved in the airway microenvironment, prolonged inflammation, and potentiated acute lung injury.
Indications for orthotopic liver transplantation in fulminant liver failure
Authors: Roger Williams, Julia Wendon
Journal: Hepatology (1994)

The decision to undertake transplantation in a patient with fulminant liver failure requires consideration of many factors so that the physician may arrive at the most appropriate course of action. There are several definitions of fulminant liver failure used in current practice, all excluding patients with chronic liver disease. In the one most recently proposed, the terms hyperacute, acute and subacute liver failure are used to categorize groups of patients with different clinical appearances and progress. Patients in the hyperacute group have a better outcome with medical treatment than others, despite deeper levels of encephalopathy. The decision to proceed to transplantation should be undertaken in patients who fulfil criteria for a poor prognosis with medical management. For two groups, Hôpital Paul Brousse, Paris, and King's College Hospital, London, criteria are based on analysis of large patient numbers, which can be applied at the bedside without recourse to complex analysis. Once a patient has been listed for transplantation, regular systems review must be undertaken because the development of irreversible multiple organ failure may preclude transplantation. Hepatectomy may occasionally have a role in stabilizing a patient awaiting a suitable organ. In less severe cases, auxiliary liver transplantation has been undertaken, and in some patients regeneration of the native liver has occurred, allowing withdrawal of immunosuppressive therapy. The results of orthotopic liver transplantation in fulminant liver failure have steadily improved over recent years, with reported 1-year survival rates of up to 80% in some series, yielding a good prognosis for certain groups of patients who previously had unacceptably high mortality (Hepatology 1994;20:5S-10S.)
Abstract 14833: Senescent Endothelial Cells Are Highly Susceptible to SARS-CoV-2 Infection, Which Might Account for the Aggravation of COVID-19 in the Elderly
Authors: Akiko Katayama, Koji Ikeda, Ekura Yamazaki, Daisuke Ueno, Masaharu Shin-ya, Eriko Ohgitani, Osam Mazda, Satoaki Matoba
Journal: Circulation (2022)

Introduction: The pandemic of coronavirus disease 2019 (COVID-19), induced by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has posed a global health emergency. COVID-19 vaccines are certainly effective to prevent infection, severe disease, and hospitalization; however, its spreading remains to be uncontrolled worldwide. The striking feature of COVID-19 is the high mortality in the elderly; every 1,000 people infected with SARS-CoV-2, around 116 will die if they are mid-seventies or older, while little will die if they are under the age of 50. Though elderly is more fragile than younger people in general, this substantial difference in mortality strongly suggest a specific factor(s) that aggravate the disease in elder people. Systemic thrombosis has been highlighted in the pathogenesis of COVID-19, and lung microangiopathy in association with endothelial cells (ECs) injury has been reported by post-mortem analysis of the lungs. Hypothesis: Senescent endothelial cells are highly susceptible to SARS-CoV-2 infection. Methods: We experimentally investigated the SARS-CoV-2 infection in ECs, and performed a comparative analysis for post-infection molecular events using young and replicative senescent ECs. Results: We identify that; 1) SARS-CoV-2 infects ECs largely through endocytosis, 2) Senescent ECs are highly susceptible to SARS-CoV-2 infection, possibly through enhanced caveolae-mediated endocytosis, 3) SARS-CoV-2 infection alters various genes expression, which could cause EC dysfunctions, 4) More genes expression is affected in senescent ECs by SARS-CoV-2 infection than in young ECs, which might causes further exacerbated dysfunction in senescent ECs, 5) SARS-CoV-2 infection significantly affected coagulation cascade only in senescent ECs. Conclusions: These data strongly suggest that sustained EC dysfunctions due to SARS-CoV-2 infection may contribute to the microangiopathy in the lungs, leading to deteriorated inflammation and thrombosis in COVID-19. Our data also suggest a possible causative role of EC senescence in the aggravated disease in elder COVID-19 patients.
Vitamin D and Cardiovascular Disease
Authors: Thomas J. Wang
Journal: Annual Review of Medicine (2016)

Vitamin D is best known for its influence on skeletal health. There is growing recognition, however, that vitamin D has nonskeletal actions, which could have important implications for understanding the consequences of vitamin D deficiency. In epidemiologic studies, vitamin D deficiency has been consistently associated with an increased risk for cardiovascular disease and hypertension. Disruption of vitamin D signaling in animal models promotes hypertension, cardiac hypertrophy, and atherosclerosis. This evidence has led to the initiation of prospective randomized trials of vitamin D supplementation in individuals at risk for cardiovascular disease. The results of these trials should help to guide strategies for screening and management of vitamin D deficiency in the clinic and at the population level.
Under greater cooperative care, childhood fear is more accommodated, but less warranted
Authors: Garriy Shteynberg
Journal: Behavioral and Brain Sciences (2023)

Abstract The target article posits that caregiver cooperation rendered heightened expression of childhood fear an adaptive response to threat. I argue that caregiver cooperation rendered childhood fear expression less accurate as a signal of actual threat, and hence less effective for harm avoidance. Further, other emotional expressions that avoid unwarranted caregiver stress may be more likely to evoke needed care.
Fear can promote competition, defensive aggression, and dominance complementarity
Authors: Nir Halevy
Journal: Behavioral and Brain Sciences (2023)

Abstract Fear can undermine cooperation. It may discourage individuals from collaborating with others because of concerns about potential exploitation; prompt them to engage in defensive aggression by launching a preemptive strike; and propel power-seeking individuals to act dominantly rather than compassionately. Therefore, accumulated evidence requires a more contextualized consideration of the link between fear and cooperation in adults.
Fearful apes or emotional cooperative breeders?
Authors: Pat Barclay, Savannah Yerman, Oliver Twardus
Journal: Behavioral and Brain Sciences (2023)

Abstract The “fearful ape hypothesis” is interesting but is currently underspecified. We need more research on whether it is specific to fear, specific to humans (or even cooperative breeders in general), what is included in “fear,” and whether these patterns would indeed evolve despite arms races to extract help from audiences. Specifying these will result in a more testable hypothesis.
Is there a human fear paradox? A more thorough use of comparative data to test the fearful ape hypothesis
Authors: Judith M Burkart, F de Oliveira Terceiro
Journal: Behavioral and Brain Sciences (2023)

Abstract Grossmann's intriguing proposal can benefit from a more thorough integration of the primate literature, particularly on neophobia. Moreover, it directly leads to strong predictions in callitrichids, the only other cooperatively breeding primates beyond humans, which may indeed be met: Being more likely to signal distress than independently breeding monkeys, and responding to such signals with approach and affiliation.
Educational Implications of Conviction Narrative Theory
Authors: Mark Sheskin, Michael Bogucki, Tomer Perry, Katie McAllister
Journal: Behavioral and Brain Sciences (2023)

Abstract Education often relies on an implicit assumption that decisions are made rationally, and focuses on situations in which there are correct answers that can be known with certainty. The proposal that decision-making is often narrative, especially in contexts of radical uncertainty, suggests important changes to education practice and new questions for education research.
Social learning and the adaptiveness of expressing and perceiving fearfulness
Authors: Karsten Olsen, Ida Selbing
Journal: Behavioral and Brain Sciences (2023)

Abstract The fearful ape hypothesis revolves around our ability to express and perceive fearfulness. Here, we address these abilities from a social learning perspective which casts fearfulness in a slightly different light. Our commentary argues that any theory that characterizes a (human) social signal as being adaptive, needs to address the role of social learning as an alternative candidate explanation.
Decisions under uncertainty are more messy than they seem
Authors: Jarno Tuominen
Journal: Behavioral and Brain Sciences (2023)

Abstract Conviction Narrative Theory (CNT) is conceptually so multifaceted as to make critical evaluation difficult. It also omits one course of action: Active engagement with the world. Parsing the developmental and mechanistic processes within CNT would allow for a rigorous research programme to put the account under test. I propose a unifying account based on active inference.
Simulation does not just inform choice, it changes choice
Authors: Karalyn F. Enz, Diana I. Tamir
Journal: Behavioral and Brain Sciences (2023)

Simulation - imagining future events - plays a role in decision-making. In Conviction Narrative Theory, people's emotional responses to their simulations inform their choices. Yet imagining one possible future also increases its plausibility and accessibility relative to other futures. We propose that the act of simulation, in addition to affective evaluation, drives people to choose in accordance with their simulations.
Infants aren't biased toward fearful faces
Authors: Andrew M. Herbert, Kirsten Condry, Tina M. Sutton
Journal: Behavioral and Brain Sciences (2023)

Grossmann's argument for the "fearful ape hypothesis" rests on an incomplete review of infant responses to emotional faces. An alternate interpretation of the literature argues the opposite, that an early preference for happy faces predicts cooperative learning. Questions remain as to whether infants can interpret affect from faces, limiting the conclusion that any "fear bias" means the infant is fearful.
Conviction Narrative Theory gains from a richer formal model
Authors: Leigh Caldwell
Journal: Behavioral and Brain Sciences (2023)

Abstract Conviction Narrative Theory (CNT) is a convincing descriptive theory, and Johnson et al.'s formal model is a welcome contribution to building more precise, testable hypotheses. However, some extensions to the proposed model would make it better defined and more powerful. The suggested extensions enable the model to go beyond CNT, predicting choice outcomes and explaining affective phenomena.
Embodied choices bypass narratives under radical uncertainty
Authors: Rouwen Cañal-Bruland, Markus Raab
Journal: Behavioral and Brain Sciences (2023)

Johnson et al. suggest that we rely on narratives to make choices under radical uncertainty. We argue that in its current version Conviction Narrative Theory (CNT) does not account for embodied, direct sensorimotor influences on choices under radical uncertainty that may bypass narratives, particularly in highly time-constrained situations. We therefore suggest to extend CNT by an embodied choice perspective.
Hominin life history, pathological complexity, and the evolution of anxiety
Authors: Walter Veit, Heather Browning
Journal: Behavioral and Brain Sciences (2023)

Abstract In order to address why the number of patients suffering from anxiety and depression are seemingly exploding in Western, educated, industrialized, rich, and democratic (WEIRD) countries, it is sensible to look at the evolution of human fearfulness responses. Here, we draw on Veit's pathological complexity framework to advance Grossmann's goal of re-characterizing human fearfulness as an adaptive trait.